The overall objective of this research proposal is to elucidate the relationship of delta-aminolevulinic acid synthetase (ALAS) activity and the aging process. Hepatic ALAS catalyzes the initial and rate-limiting step in heme biosynthesis and thus may control intracellular heme levels. As a result, the content of many heme proteins whose synthesis and degradation is regulated by heme, may also be affected by the activity of ALAS. Furthermore, the activity of hepatic ALAS is increased several-fold by acute ethanol intoxication as well as by a variety of chemicals which also cause an experimental porphyria. During the past two years the purificaton of ALAS had been achieved in our laboratory and monovalent antibodies have been obtained. Furthermore, a 50-70% decrease in ALAS activity was observed in liver, heart and brain of aging rats when compared to young controls. The underlying age-related changes which result in the lowered ALAS activity will be studied, using immunological techniques. In addition, we will establish whether an increase in ALAS protein in mitochondria accompanies the increase in activity observed in porphyric animals.